Mechanism of interaction between Wuzhi capsules and CYP3A4 based on molecular docking and surface plasmon resonance
Objective To determine the mechanism of Wuzhi capsules affecting the metabolism of other drugs through CYP3A4.Methods Molecular docking was used to screen the mechanism of six main active components of Wuzhi capsules:schisandrin A,schisandrin B,schisandrin C,schisandrol A,schisandrol B,and schisantherin A,along with the positive control drug itraconazole with CYP3A4.The docking function of Molecular Operating Environment software was used to obtain the docking scores(S).Subsequently,surface plasmon resonance(SPR)was used to assess the affinity of each active component and the positive control with CYP3A4.Results The molecular docking showed that the six main components of Wuzhi capsules were highly complementary to CYP3A4 in terms of space structure,among which schisantherin A had the lowest S-value of-8.4517.SPR showed that schisantherin A had the strongest binding affinity to CYP3A4,with a Kd of 3.21 × 10-8 mol·L-1,followed by schisandrin A.The affinity of schisandrin C,and schisandrol A propin to CYP3A4 was relatively weak.In the affinity fitting curves,the six main components of pentosan capsules had better affinity with CYP3A4.Conclusion Schisantherin A shows the strongest binding to CYP3A4.As compared with the itraconazole,other components also show strong binding ability to CYP3A4,which may be the main reason how Wuzhi capsules affect the metabolism of other drugs through CYP3A4.
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